Percutaneous drug delivery apparatus

ABSTRACT

An implantable percutaneous fluid delivery device is described that includes a subcutaneous base portion having one or more ports for supplying fluid to one or more implanted catheter devices and a percutaneous portion including an extracorporeal surface. The one or more ports of the subcutaneous base portion are accessible from the extracorporeal surface of the percutaneous portion. The subcutaneous base portion is at least partially insertable into a complementary recess formed in a bone, the subcutaneous base portion including one or more features for gripping the internal surface of such a complementary recess thereby directly anchoring the subcutaneous base portion to the bone. The device may be used to route fluid to neurosurgical catheters optionally via a router unit.

This is a Continuation of application Ser. No. 13/575,769, filed Jul.27, 2012, which is a National Stage of Application No.PCT/GB2011/000183, filed Feb. 11, 2011. The prior applications,including the specification, drawings and abstracts are incorporatedherein by reference in their entirety.

BACKGROUND

The present invention relates to drug delivery apparatus and inparticular to neurological drug delivery apparatus comprising a skullmountable percutaneous fluid delivery device.

Implantable drug delivery systems are known for the treatment ofneurological conditions where the blood brain barrier prevents manysystemically administered drugs from reaching the desired target, orwhere the delivery of drugs or therapeutic agents to targets other thanthe desired target may produce unacceptable side affects. In particular,it is known to deliver drugs and other therapeutic agents directly intothe brain parenchyma via one or more implanted catheters. Examples ofthis type of therapy include the infusion of gamma-amino-butyric acidagonists into an epileptic focus or pathway that will block itstransmission, the delivery of cytotoxic agents directly into a braintumour, and the infusion of neurotrophic agents for the protection andrepair of failing or damaged nerve cells. The infusion of suchneurotrophic agents can be used to treat a variety of neurodegenerativedisorders including Parkinson's disease, Alzheimer's disease andAmyotrophic Lateral Sclerosis, and may also be useful in stimulating therepair of damaged neural tissue after injury from trauma, stroke orinflammation.

Fully implantable neurological drug delivery systems have been used formany years. A pump is typically located in the abdomen and tubing istunnelled subcutaneously to implanted intraparenchymal catheters.Examples of implantable drug delivery pumps for delivery of therapeuticagents to the brain parenchyma are shown, for example, in U.S. Pat. No.4,013,074, U.S. Pat. No. 4,692,147, U.S. Pat. No. 5,752,930 andWO2004/105839.

It is also known to provide so-called percutaneous access devices thatprovide a fluid connection between the inside and the outside of thebody. Examples of devices that can be used for providing external accessto a subject's blood stream are described in US2004/0249361, U.S. Pat.No. 6,607,504 and U.S. Pat. No. 5,098,397. A stabilised percutaneousaccess device for neurological applications has also been describedpreviously in WO2008/062173. Transcutaneous fluid transfer apparatuscomprising a plate that can be fixed to the skull using bone screws isdescribed in WO97/49438. A percutaneous transferring device that can bescrewed to bone is also disclosed in WO99/34754.

SUMMARY

According to a first aspect of the present invention, an implantablepercutaneous fluid delivery device is provided that comprises; asubcutaneous base portion comprising one or more ports for supplyingfluid to one or more implanted catheter devices, and a percutaneousportion comprising an extracorporeal surface, the one or more ports ofthe subcutaneous base portion being accessible from the extracorporealsurface of the percutaneous portion, wherein the subcutaneous baseportion is at least partially insertable into a complementary recessformed in a bone, the subcutaneous base portion comprising one or morefeatures for gripping the internal surface of such a complementaryrecess thereby directly anchoring the subcutaneous base portion to thebone.

The present invention thus relates to an implantable percutaneous fluiddelivery device or port unit for use in delivering fluid, such astherapeutic agents, to selected targets within the body. The implantablepercutaneous fluid delivery device has one or more outlets or ports thatare separately connectable to one or more implanted catheter devices.The implantable percutaneous fluid delivery device is particularlysuited for use in delivering therapeutic agents to targets within thebrain using one or more associated implanted intraparenchymal catheterdevices.

The implantable percutaneous fluid delivery device comprises asubcutaneous base portion comprising one or more ports for supplyingfluid to one or more implanted catheter devices. The term subcutaneousas used herein is intended to define a location below the outer surfaceof the skin. As described below, the subcutaneous base portion ispreferably implantable below all of the skin A percutaneous portion isalso provided as part of the device that extends from the subcutaneousbase portion and comprises an extracorporeal surface. As would beunderstood by those skilled in the art, when implanted a percutaneousdevice crosses the skin to provide a connection between the inside andoutside of the body. The one or more ports of the subcutaneous baseportion are accessible from the extracorporeal surface of thepercutaneous portion; in other words, the extracorporeal surface (i.e. asurface accessible from outside of the body) provides fluidic access tothe one or more outlet ports of the subcutaneous base portion of thedevice. It should be noted that the subcutaneous base portion andpercutaneous portion may be formed together or may be formed as separatecomponents that are attached together before use.

The subcutaneous base portion of the device of the first aspect of thepresent invention is at least partially insertable into a complementaryrecess formed in a bone (e.g. a skull bone). The subcutaneous baseportion also comprises one or more features for gripping the internalsurface or wall(s) of such a recess thereby directly securing oranchoring the subcutaneous base portion to the bone. In this manner, amechanical fit (e.g. a friction fit) of the device can be obtainedimmediately on implantation without the need for bone screws or thelike. Over time, any mechanical stresses will dissipate as the bonegrows or reforms. For longer term (e.g. chronic) applications, it isthus preferred that at least part of the subcutaneous base portionosseointegrates after implantation. As described in more detail below,it is thus preferred that some or all of the subcutaneous base portionintegrates with bone after implantation thereby anchoring or securingthe device in place for the longer term. Such a bone anchored device hasthe advantage that it can be more securely attached to a subject than afloating or skin stabilised port. Furthermore, there is no mechanicalload placed on soft tissue when external fluid connectors are attachedto the extracorporeal surface of the device. This reduces thepossibility of skin tears or damage that may increase the risk ofinfection.

Advantageously, the subcutaneous base portion is shaped to provide afriction fit with a complementary recess formed in a bone. The baseportion may, for example, have a rough surface and/or other surfacefeatures (e.g. ridges, protrusions etc) that engage and grip the recessformed in the bone. For example, the device may be secured in place by apush-fit or press-fit action. The device may be forced into tightengagement with the bone recess using an impactor or other tool.Providing a friction fit and optionally promoting osseointegrationpermits a simpler surgical implantation procedure and a more reliableattachment of the device to a subject than can be achieved using glue,screws or the like.

As mentioned above, it is preferred, but not essential, that at leastpart of the subcutaneous base portion osseointegrates. In other words,the bone conveniently integrates with (e.g. grows into, onto and/orthrough) the subcutaneous base portion after implantation. Preferably,the base portion comprises a rough surface that promotesosseointegration. The base portion may additionally or alternativelycomprise a coating that promotes osseointegration. For example, acoating of plasma sprayed titanium and/or hydroxyapatite on the outersurface of the subcutaneous base portion may be provided. Promotingosseointegration in this manner has the advantage of preventing thesubcutaneous base portion moving (e.g. slipping or twisting) or becomingdetached from the bone after implantation. Promoting osseointegrationis, however, superfluous when the device is used for short term (e.g.acute) surgical interventions.

When implanted, at least part (and preferably most) of the subcutaneousbase portion is located below the outer surface of a bone. The devicethus preferably includes a feature or features that allow the depth ofinsertion of the device into an appropriate recess formed in a bone tobe predefined. Advantageously, the base portion comprises a protrudinglip or step(s) for engaging the outer surface of a bone around theperiphery of a recess formed in that bone. Such a lip thus sits on theoutermost bone surface when inserted and, as well as setting the depthof insertion, also allows the device to be implanted in a hole thatpasses all the way through a bone.

Advantageously, the subcutaneous base portion comprises a first partthat is attached or attachable to the percutaneous portion.Conveniently, an elongate section is provided that protrudes from thefirst part. Preferably, when the device is anchored to a bone the body,the whole of the elongate section is located within a recess or trenchformed in that bone. This allows the elongate section to be completelyimplanted within the bone; the recess or trench containing the elongatesection may also be backfilled with bone chippings to bury the elongatesection. In this manner, the elongate portion lies below the outersurface of the bone when implanted. The elongate section may comprise arigid, e.g. tubular, member. The elongate section may comprise a lengthof tubing that protrudes from the first part and terminates at a fluidconnection to a supply tube. Alternatively, the elongate section maycomprise the proximal end of a longer section of tubing; for example, anend of tubing that leads to a implantable fluid router or the like.Providing such a protruding elongate section (i.e. that can be buried ina bone recess) also helps prevent rotation of the device relative to thebone after implantation (e.g. when establishing fluid connections).

Advantageously, the subcutaneous base portion comprises a second part,the first and second parts of the subcutaneous base portion beingconnected by the elongate section. The first and second parts may belocatable in separate, spaced apart, recesses formed in the bone. Achannel or trench between the first and second parts may also be formedin the bone for receiving the elongate section. The second(subcutaneous) part may include one or more filters (e.g. air and/orbacterial filters). The second part may also include one or more tubegrips and/or tube connectors that enable one or more supply tubes and/orcatheter devices to be operatively connected to the implantablepercutaneous fluid delivery device. The second part may include skullfixation means, such as flanges, ribs or other fixtures, that allow itto be attached (e.g. push-fitted or screwed) to the bone. Securing boththe first and second parts of the subcutaneous base portion directly tothe bone has the advantage that the device can be more firmly anchoredin place and is less likely to become detached with time and/or use.

The one or more fluid channels of the ports preferably extend throughthe elongate section. In this manner, the buried elongate section mayseparate the percutaneous portion from the part (e.g. the second part)of the subcutaneous base portion to which the supply tube(s) carryingfluid to the associated catheter devices are attached. Advantageously,the elongate section is at least 5 mm long. The elongate section is morepreferably at least 10 mm long, more preferably at least 20 mm long andmore preferably at least 30 mm long.

The elongate section has been found to act as a barrier to any infectionpresent at the percutaneous portion (i.e. the location where infectionis most likely to occur) from passing to the implanted catheter devices.In particular, the skin can be thinned in the region of the elongatesection during implantation of the device to promote bio-integration ofthe dermis with the periosteum. This local bio-integration of the skinwith the periosteum effectively provides a living seal between the boneand the skin that reduces the risk of infection present at thepercutaneous portion from spreading along the elongate section.Providing such an elongate section has thus been found to provide aneffective infection barrier that helps prevent any infection present atthe device-skin interface from reaching catheter devices attached to theimplantable percutaneous fluid delivery device.

The implantable percutaneous fluid delivery device may include a singleport that provides fluidic access to a single catheter device. However,as the device is anchored directly to bone, it is particularly suitedfor use with a plurality of ports. In particular, the greater forcerequired to establish a plurality of fluid connections (e.g. by forcinga plurality of needles through a septum) is passed directly to the boneand there is minimal mechanical load on the soft tissue that could causetearing and thereby increase the risk of infection. Advantageously, thedevice comprises two or more ports. More preferably, the device maycomprise at least three, at least four or more than four ports. Eachport may be in fluid communication with a separate catheter device,optionally via an implantable router unit or other fluid routing device.

The device may comprise one or more components for filtering any fluidit receives. For example, the device may comprise a bacterial filterand/or a gas (e.g. air) filter or vent. The device may also includevarious seals, flow control components and tubes or tube grips etc.

Advantageously, the subcutaneous base portion comprises at least onesubcutaneous fluid inlet. Each subcutaneous fluid inlet is preferablyfor receiving fluid from a remotely implanted pump (e.g. from a pumpimplanted in the abdomen). A subcutaneously tunnelled tube may beprovided to supply fluid to the subcutaneous fluid inlet from theremotely implanted pump. Fluid received at the subcutaneous fluid inletis preferably routable to the one or more ports. For example, the fluidreceived at the subcutaneous fluid inlet may be routed to each, or some,of the one or more ports.

The subcutaneous fluid inlet may receive the fluid under pressure (e.g.at a constant pressure). The device may include one or more flow ratecontrollers to control the flow rate of fluid from the subcutaneousfluid inlet to the one or more ports. The fluid received at thesubcutaneous fluid inlet may be a non-therapeutic or carrier fluid; e.g.it may comprise buffered saline, artificial CSF or another suitableinert fluid.

The fluid pumped to the subcutaneous fluid inlet may be from a reservoir(e.g. a reservoir provided as part of, or separately from, the pump) orcollected from the body cavity. For example, the fluid may comprise CSFcollected using an implanted intracranial shunt for neurologicalapplications. Providing such a subcutaneous fluid inlet allows aconstant flow of fluid (e.g. at a low flow rate of around 0.2 ml perhour) to the implanted catheter device. This is especially advantageousfor neurological applications that use implanted catheters deviceshaving a small internal diameter of, say, less than 0.25 mm; theconstant fluid flow has the advantage of preventing such cathetersbecoming blocked during use.

The subcutaneous fluid inlet may be in permanent fluid communicationwith the one or more ports. Advantageously, accessing the one or moreports via the extracorporeal surface substantially blocks the flow offluid to the one or more ports from the subcutaneous fluid inlet. Inother words, accessing the ports via the extracorporeal surface (e.g. todeliver a therapeutic agent via the implanted catheter devices) mayreduce or obstruct the fluid flow from the subcutaneous inlet to the oneor more ports. The device may include one or more valves that block thefluid flow when the ports are accessed from the extracorporeal surface.The extracorporeal surface thus allows the flow of carrier fluid to bestopped or bypassed whilst the therapeutic agent is delivered.

The percutaneous portion of the device, and in particular the interfacebetween the skin and the device, is the most likely site where infectionmay occur. It is thus preferred that at least some of the percutaneousportion comprises a peripheral surface that encourages tissue (skin)ingrowth. For example, a lower region of the peripheral surface of thepercutaneous portion may be porous or roughened. This may be achieved bymaking at least part of the percutaneous portion from a porous materialsuch as porous titanium, by coating it with a porous/rough material(e.g. hydroxyapatite or a nano fibrous matrix) or by texturing thesurface.

Preferably, the surface of the percutaneous portion is rough where, whenimplanted, it contacts the dermis. This helps to reduce the ingress ofbacteria or other microbes by encouraging the dermis to form a tightjunction with the surface of the percutaneous portion. Furthermore, asthe mechanical load imparted on the device is transmitted directly tothe bone, accessing the ports via the extracorporeal surface does notload or disturb this tissue interface thereby also reducing the chancesof infection. Preferably, at least some of the percutaneous portioncomprises a smooth peripheral surface. For example, an upper region ofthe peripheral surface of the percutaneous portion may be smooth (e.g.coated with a diamond like coating). Preferably, the surface of thepercutaneous portion is smooth where, when implanted, it lies adjacentthe epidermis. The smooth surface inhibits tissue in-growth and can bekept clean thereby further reducing the risk of infection of theunderlying dermis.

As described above the one or more ports of the device are accessiblefrom the extracorporeal surface of the percutaneous portion. The devicepreferably comprises a seal to prevent or reduce the ingress ofmicrobes. Any appropriate seal may be used. Conveniently, the seal is inthe form of a bung, made from, for example, rubber or silicone.Advantageously, the seal comprises an antimicrobial (e.g. antibacterial)material; e.g. the rubber or silicon bung may be silver impregnated. Theextracorporeal surface of the device is preferably arranged to allowaccess to the one or more ports through or via the seal. For example,the extracorporeal surface may be provided with one or more apertures ormay be removable. In use, a therapeutic agent may be introduced to theport by, for example passing a needle through the aperture and throughthe bung and injecting the agent into the port. The seal may bereplaceable (e.g. under appropriate sterile conditions) from theextracorporeal side of the device.

The above described device may be used for delivering therapeuticagent(s) to the central nervous system (e.g. to the brain or spinalcord). Advantageously, the above described device is used for deliveringtherapeutic agent(s) to the brain. The present invention may thuscomprise neurological apparatus comprising a percutaneous fluid deliverydevice as described above. The apparatus may also comprise one or moreintraparenchymal catheter devices that can be implanted to deliver fluidto one or more target sites within the brain parenchyma.

Advantageously, the percutaneous fluid delivery device is connected tothe one or more intraparenchymal catheter devices via an implantablerouter unit. The implantable router unit may have one or more inlets forrouting fluid received from the percutaneous fluid delivery device toone or more outlets that are connected to the one or more catheterdevices. The apparatus conveniently comprises a supply tube having oneor more lumens. Preferably, the supply tube is at least 5 cm long, morepreferably at least 10 cm long and more preferably at least 15 cm long.Providing such a length of supply tube acts to separate the router unitfrom the percutaneous fluid delivery device thereby reducing the risk ofinfection reaching the router unit from the percutaneous fluid deliverydevice. The one or more ports of the percutaneous fluid delivery devicemay be connected to the one or more inlets of the router unit via thesupply tube. Preferably, the percutaneous fluid delivery devicecomprises a plurality of ports connected to a plurality of catheterdevices via a multi-lumen supply tube and an implantable router unithaving a plurality of inlets that are each separately connected to oneof plurality of outlets.

Advantageously, the implantable router unit comprises one or more fluidfiltration components. For example, the implantable router unit maycomprise a gas (e.g. air) filter or vent and/or a bacterial filter. Ifthe implantable router unit has a plurality of separate fluid pathstherethrough (e.g. if it comprises a plurality of inlets that are eachconnected to one of a plurality of outlets) it is preferred thatseparate filtration is applied to each fluid path. Providing filtrationas part of the implantable router unit has the advantage that thefiltration occurs in close proximity to the catheter devices. The lengthof the path from the filter to the point of fluid delivery is thusminimised thereby minimising the introduction of contaminants or airinto the fluid during its transmit through the fluid delivery apparatus.

Advantageously, the apparatus comprises an external (to the body) fluidconnector unit for cooperating with the extracorporeal surface of thepercutaneous fluid delivery device to provide fluid communication withthe ports. The extracorporeal surface and the external fluid connectorunit may be configured to mate to provide the required fluidic link(s)with the one or more ports. As mentioned above, the extracorporealsurface may provide access to a plurality of ports. The external fluidconnector unit may then comprise, for example, a plurality of needlesthat penetrate a septum of the percutaneous fluid delivery device toprovide separate fluidic access to each of the ports. Preferably, if theextracorporeal surface provides access to a plurality of ports, one ormore alignment features are provided to ensure the fluid connector unitis attachable to the extracorporeal surface in only a single, unique,orientation. The alignment feature may comprise the shape of the matingparts of the extracorporeal surface and the external fluid connectorunit and/or alignment prongs and/or any other suitable physicalfeatures. The provision of such alignment features ensures that thefluid lines of the fluid connector unit are always placed in fluidcommunication with the same ports of the percutaneous fluid deliverydevice. A suitable fluid connector is described in WO2007/104961.

A locking mechanism may be provided to lock the fluid connector unit tothe extracorporeal surface of the percutaneous fluid delivery device.This may be used to prevent unwanted or uncontrolled detachment of thefluid connector unit from the percutaneous fluid delivery device. Theexternal fluid connector unit may be connected to external pump(s) or tosyringes or other means of pumping therapeutic agent through theapparatus. The external fluid connector unit may also include in-linefilters. The invention also extends to a separate fluid connector unitfor cooperating with the extracorporeal surface of a percutaneous fluiddelivery device of the type described above in order to provide fluidcommunication with the one or more ports of said device.

The percutaneous fluid delivery device may also comprise a protectivecap. The protective cap may be arranged to releasably engage theextracorporeal surface of the percutaneous fluid delivery device. Whenattached, the cap may prevent access to the ports of the device. If thepercutaneous fluid delivery device comprises a septum seal, the cappreferably protects the septum seal. A locking mechanism may be providedto lock the protective cap to the extracorporeal surface of thepercutaneous fluid delivery device. This locking mechanism may be usedto prevent unauthorised or unwanted detachment of the protective capfrom the percutaneous fluid delivery device (e.g. by a patient). Thepresent invention also extends to a protective cap for a percutaneousfluid delivery device as described above. Warnings or other indicationsmay be marked on the cap. The cap or percutaneous fluid delivery devicemay include an electronic tag that stores information on the implantedfluid delivery device and/or treatment information.

In addition to providing a percutaneous fluid delivery device having oneor more ports through which fluid can be routed, one or more furtherconnector functions may be provided. For example, the device may provideone or more electrical connections and/or one or more opticalconnections. Advantageously, the one or more ports of the device maythemselves be used to transmit electricity, light or ultrasound energyvia the fluid medium.

According to a further aspect of the invention, a jig is provided forimplanting a percutaneous fluid delivery device as described above. Thejig preferably provides a template for cutting a recess in bone (e.g. ina skull bone) into which the subcutaneous base portion of thepercutaneous fluid delivery device can be friction fitted. The jig mayinclude temporary attachment means (e.g. an aperture for receiving bonescrews) that allow it to be secured to bone whilst the appropriaterecess is formed. A drill or other bone cutting device may be providedto form the recess in the bone using the jig as the template. Thepresent invention, in a yet further aspect, also relates to a surgicalmethod of implanting a percutaneous fluid delivery device of the typedescribed above. Preferably, such a surgical procedure employs the abovedescribed jig. For neurological applications, the percutaneous fluiddelivery device is preferably implanted in the skull adjacent the ear.The method may also include locally thinning the scalp in the regionwhere the device is implanted.

According to a further aspect of the invention, an implantablepercutaneous fluid delivery device is provided that comprises asubcutaneous base portion comprising one or more ports for supplyingfluid to one or more implanted catheter devices, and a percutaneousportion comprising an extracorporeal surface, the one or more ports ofthe subcutaneous base portion being accessible from the extracorporealsurface, the subcutaneous base portion comprising a first part that isattached to the percutaneous portion and an elongate section thatprotrudes from the first part, wherein, when the device is implanted inthe body, at least part of the elongate section is located (e.g. buried)within a recess formed in the bone. Preferably, the subcutaneous baseportion further comprises a second part, the first part being connectedto the second part by the elongate section. Conveniently, when thedevice is anchored to a bone the body, the whole of the elongate sectionis located within a recess or trench formed in that bone. Each of theone or more ports preferably comprises a fluid channel that extends fromthe first part to the second part though the elongate section. Thedevice may also include any one or more of the other features that aredescribed herein.

According to a further aspect of the invention, an implantablepercutaneous fluid delivery device is provided that comprises asubcutaneous base portion comprising one or more ports for supplyingfluid to one or more implanted catheter devices and a percutaneousportion comprising an extracorporeal surface, the one or more ports ofthe subcutaneous base portion being accessible from the extracorporealsurface of the percutaneous portion, wherein the subcutaneous baseportion is at least partially insertable into a complementary recessformed in a bone and at least part of the subcutaneous base portionosseointegrates following implantation. Preferably, the subcutaneousbase portion comprises at least one of a rough surface and a coatingthat promotes osseointegration. The device may also include any one ormore of the other features that are described herein.

An implantable router unit is also described herein that comprises oneor more inlets and one or more outlets, wherein fluid is routable fromthe one or more inlets to the one or more outlets. The router unit maycomprise an air filter for removing air from fluid routed from the oneor more inlets to the one or more outlets. The implantable router unitmay include a bacterial filter. Preferably, the implantable router unitcomprises a plurality of inlets that are each separately connected toone of the plurality of outlets. If the implantable router unit has aplurality of separate fluid paths therethrough (e.g. if it comprises aplurality of inlets that are each connected to one of a plurality ofoutlets) it is preferred that separate air filtration is applied to eachfluid path. For example, each fluid path may include a separate filterchamber. Conveniently, the filter (e.g. each filter chamber) comprisesan hydrophobic layer and a hydrophilic layer to provide a gas (e.g. air)venting or filtering function. In other words, the filter separates andremoves any gas (e.g. air) from the liquid therapeutic agent beingdelivered. A membrane or diaphragm may also be provided (e.g. adjacentthe hydrophobic layer) through which any vented air dissipates into thebody cavity. The implantable router unit may be provided as part of acatheter device. For example, an implantable router unit having a singleinlet and single outlet may be incorporated in the head of anintra-parenchymal catheter.

An implantable percutaneous fluid delivery device is also describedherein that comprises; a subcutaneous base portion comprising one ormore ports for supplying fluid to one or more implanted catheterdevices, and a percutaneous portion extending from the subcutaneous baseportion, wherein the percutaneous portion comprises an extracorporealsurface and the one or more ports of the subcutaneous base portion areaccessible from the extracorporeal surface. The subcutaneous baseportion may comprise a subcutaneous fluid inlet for receiving fluid froma remotely implanted pump, wherein fluid received at the subcutaneousfluid inlet is routable to the one or more ports. Advantageously,accessing the one or more ports via the extracorporeal surfacesubstantially blocks the flow of fluid to the one or more ports from thesubcutaneous fluid inlet. The subcutaneous base portion may also beanchored to the bone of a subject and at least part of the subcutaneousbase portion may promote osseointegration. The device may also includeany of the other features that are described herein.

An implantable percutaneous fluid delivery device is also describedherein that comprises a subcutaneous base portion comprising one or moreports for supplying fluid to one or more implanted catheter devices, anda percutaneous portion extending from the subcutaneous base portion,wherein the percutaneous portion comprises an extracorporeal surface andthe one or more ports of the subcutaneous base portion are accessiblefrom the extracorporeal surface, the subcutaneous base portioncomprising a first part that is attachable to the percutaneous portionand an elongate section that protrudes from the first part, the fluidchannels defined by the ports extending through the elongate section,wherein, when the device is implanted in the body, the whole of theelongate section is located within a recess formed in the bone.

An implantable percutaneous access device is also described herein thatcomprises; a subcutaneous base portion comprising one or moreconnections to one or more implanted devices, and a percutaneous portionextending from the subcutaneous base portion, wherein the percutaneousportion comprises an extracorporeal surface and the one or moreconnections of the subcutaneous base portion are accessible from theextracorporeal surface. The subcutaneous base portion is preferablydirectly anchorable to a bone of a subject and is configured to promoteosseointegration after implantation. The one or more connectionsprovided by the device may comprise at least one of an optical,electrical or fluidic connection. Advantageously, the subcutaneous baseportion comprises a plurality of connections to a plurality of implanteddevices.

An implantable percutaneous fluid delivery device is thus describedherein. The device may comprise a subcutaneous base portion. Thesubcutaneous base portion may comprise one or more ports for supplyingfluid to one or more implanted catheter devices. A percutaneous portionmay be provided. The percutaneous portion may extend from thesubcutaneous base portion. The percutaneous portion may comprise anextracorporeal surface. The one or more ports of the subcutaneous baseportion are preferably accessible from the extracorporeal surface. Thesubcutaneous base portion is advantageously directly anchorable to abone of a subject. The device may include any one or more of the otherfeatures that are described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described, by way of example only, withreference to the accompanying drawings in which;

FIG. 1 shows implantable neurological drug delivery apparatus of thepresent invention,

FIG. 2 illustrates the device of FIG. 1 implanted in a subject,

FIGS. 3 a-3 d shows various sections through the percutaneous drugdelivery port of the apparatus of FIG. 1,

FIG. 4 show the percutaneous drug delivery port of the apparatus of FIG.1 when assembled,

FIGS. 5 a-5 c show one method for fabricating the percutaneous drugdelivery port of the apparatus of FIG. 1,

FIG. 6 shows a guide device for implanting the drug delivery port shownin FIGS. 1 to 5,

FIGS. 7 a-7 g show a surgical technique for implanting the neurologicaldrug delivery apparatus of FIG. 1,

FIG. 8 illustrates a further implantable neurological drug deliveryapparatus of the present invention,

FIGS. 9 a-9 c show in more detail the percutaneous drug delivery port ofthe apparatus of FIG. 8,

FIG. 10 show a further implantable neurological drug delivery apparatusof the present invention

FIG. 11 shows the air/bacterial filter and percutaneous drug deliveryport of the apparatus of FIG. 10,

FIG. 12 is an exploded view of the air/bacterial filter shown in FIGS.10 and 11,

FIG. 13 shows a further implantable neurological drug delivery apparatusof the present invention,

FIG. 14 illustrates a further implantable neurological drug deliveryapparatus of the present invention having a separate filter unit,

FIG. 15 shows a further implantable neurological drug delivery apparatusof the present invention having a CSF pump,

FIG. 16 illustrates a bone mounting technique for securing apercutaneous drug delivery port to the skull,

FIG. 17 shows the device of FIG. 16 when implanted in a skull,

FIG. 18 shows a valved percutaneous drug delivery port,

FIG. 19 shows the valved percutaneous drug delivery port of FIG. 18 witha needle for delivering therapeutic agent inserted, and

FIG. 20 is an exploded view of the valved percutaneous drug deliveryport shown in FIGS. 18 and 19.

DETAILED DESCRIPTION OF EMBODIMENTS

Referring to FIG. 1, implantable neurological drug delivery apparatus ofthe present invention is shown. The apparatus comprises a constantpressure pump 2 that includes an internal reservoir and has an outlet 4connected to the first end of a single lumen supply tube 6. Although aconstant pressure pump 2 is shown, it should be noted that anyimplantable pump (e.g. a constant or programmable flow rate pump) can beemployed. The second end of the supply tube 6 is connectable to theinlet 8 of a port unit 10. The port unit 10 comprises two outlets thatare linked to the two inlets of a router unit 12 by a dual-lumen supplytube 14. The router unit 12 comprises two outlets 16, each in fluidcommunication with a respective lumen of the supply tube 14, that areeach connectable to a neurological catheter device 18.

The port unit 10 comprises a subcutaneous portion 20 and a percutaneousportion 22 that has an extracorporeal surface 24. The subcutaneousportion 20 is suitable for at least partial insertion into anappropriately shaped recess formed in the skull. In particular, thesubcutaneous portion 20 is coated with a material that promotesbiointegration with bone after implantation and will thus become securedto the skull without the need for bone screws or the like. In otherwords, the subcutaneous portion 20 is osseointegrating (also termedosteointegrating). In this example, the coating provided on the externalsurface of the subcutaneous portion 20 comprises plasma sprayed titaniumcombined with hydroxy-apatite. Other coatings or surface finishes may beprovided to produce a similar effect.

The subcutaneous portion 20 may be formed as a single component butcomprises three discrete functional parts. In particular, a firstsubstantially cylindrical part 26 of the subcutaneous portion 20 isconnected to a second substantially cylindrical part 28 by an elongatejoining section 30. As will be described in more detail below withreference to FIG. 3, the second substantially cylindrical part 28 has aninlet 8 for receiving carrier fluid from the pump outlet 4 and an exitfor a dual-lumen supply tube 14 that comprise a separate lumen forsupplying fluid to each of the two catheters 18 via the router unit 12.The first substantially cylindrical part 26 is also attachable to thepercutaneous portion 22 thereby allowing external access to the separatefluidic pathways to the two catheter devices 18. In particular, theextracorporeal surface 24 comprises two sealed access ports that permitfluid (e.g. a drug or other therapeutic agent) to be injected into thefluid stream that runs from the pump 2 to the catheter devices 18.

An external fluid connector unit 23 is also provided that is releasablyattachable to the extracorporeal surface 24 of the percutaneous portion22. When the connector unit 23 is attached or mated with the port unit10, a pair of protruding needles 29 penetrate the seal and therebyprovide separate fluidic access to the two ports of the port unit 10.The needles of the fluid connector unit 23 may be separately connectedto different channels of an external drug pump 27 or individual pumpsvia a multi-lumen tube 25. In this manner, the fluid connector unit 23provides separate fluidic access to the different ports of the port unit10 to enable the delivery of therapeutic agents or the like to thecatheter devices 18. The fluid connector unit 23 may be attachable tothe extracorporeal surface 24 in only one orientation to ensure the sameneedle always accesses the same port. A locking mechanism may also beprovided to lock the fluid connector unit 23 to the extracorporealsurface 24 as and when required.

The first substantially cylindrical part 26 is connected to the secondsubstantially cylindrical part 28 by the elongate joining section 30.The elongate joining section 30 comprises multiple lumens (in this casethree) that provide the necessary fluidic pathways between the first andsecond substantially cylindrical parts 26 and 28. In addition, theprovision of such an elongate joining section 30 has the benefit ofreducing the infection risk. Infection risk is further reduced byspacing the port unit 10 apart from the router unit 12. This isdescribed in more detail below.

Referring to FIG. 2, the drug delivery apparatus described withreference to FIG. 1 is illustrated when implanted in the body. Theconstant pressure pump 2, which may comprise a diaphragm pump of knowntype, is not shown in FIG. 2 but is implanted in the abdomen. The supplytube 6 running from the pump 2 is tunnelled under the skin to the headof the subject. The port unit 10 is affixed within an appropriatelydimensioned recess formed in the bone of the skull adjacent the ear; atechnique for attaching the port unit to the skull is described in moredetail below with reference to FIGS. 6 and 7 a-7 g. The supply tube 6 isconnected to the inlet 8 of the port unit 10 and the dual-lumen supplytube 14 exiting the port unit 10 is subcutaneously tunnelled under thescalp to the router unit 12. The router unit 12 is secured to the skull,for example using bone screws, in the vicinity of the point where thecatheter devices 18 pass through holes in the skull and enter the brainparenchyma.

The constant pressure pump 2 contains a reservoir that stores a carrierfluid, such as saline (e.g. buffered saline) or artificial cerebrospinalfluid (CSF). The pump 2 may be refillable in a known manner bypercutaneous injection into a refill port provided on a surface of thepump 2. After implantation, the pump 2 supplies carrier fluid underpressure to the port unit 10 via the supply tube 6. The port unit 10 isarranged to continuously direct a small flow of carrier fluid to each ofthe catheter devices 18 via the dual-lumen supply tube 14 and routerunit 12. The distal end 40 of each catheter device 18 is accuratelypositioned within the brain parenchyma at a required target site.Examples of suitable catheter devices are described in WO03/077785.Techniques for locating the catheters adjacent the required target sitesin the brain are described in U.S. Pat. No. 6,609,020 and WO003/077784.The contents of these documents are hereby incorporated by reference.

For the majority of the time after implantation, the drug deliveryapparatus is arranged to pump small volumes of carrier fluid into thebrain parenchyma via the catheter devices 18. The constant, orsubstantially constant, flow of carrier fluid reduces the chance of thecatheter devices 18 becoming occluded due to tissue in-growth. Thisallows the chronic implantation of catheter devices that include finetubes having an outer diameter of less than 0.25 mm When the delivery oftherapeutic agents is required, the extracorporeal surface 24 of thepercutaneous portion 22 of the port unit 10 provides separate access tothe fluidic pathways to each catheter device 18 and thus permits therequired dosage of therapeutic agent to be delivered to the targetsite(s). Such delivery of therapeutic agent may be performedcontinuously (e.g. over a period of a few hours or days) through eachcatheter in parallel. Alternatively, the delivery of therapeutic agentmay be performed serially (e.g. through each catheter in turn) tominimise any side effects associated with the delivered agent.

For many years, fully implantable drug delivery systems have beenpreferred for neurological applications to minimise the chances of aninfection bypassing the blood-brain barrier and entering the brainparenchyma at the point the barrier is penetrated by a catheter. Suchfully implantable system have however been found to have a number ofdisadvantages; for example, the storage capacity can be limited andproblems often arise delivering drugs that have a short shelf-life orneed to be stored in a certain environment (e.g. at a certaintemperature). The use of a single implanted pump also does not providethe flow control that is needed when delivering fluid in precise volumesto different site using multiple catheters. It can also be difficult toaccess a refill port of a subcutaneously implanted pump, especially inobese patients, and any subcutaneous leakage of therapeutic agent canprovoke an immune response to such agents. Although percutaneous accessports or refill ports have been proposed previously, such ports tend tobe implantable in the torso, thereby requiring long lengths of supplytubing that increase the dead volume of the system. This additional deadvolume can reduce the control over drug delivery thereby reducingtreatment efficacy in certain circumstances.

The drug delivery apparatus illustrated in FIGS. 1 and 2 includes a portunit 10 that attached to the skull, but the apparatus is configured suchthat the inclusion of the percutaneous portion 22 does not introduce anunacceptable increase in the risk of an infection bypassing theblood-brain barrier. A number of features of the apparatus minimise thisinfection risk and, as described below, some or all of such features maybe included in the apparatus as required.

The subcutaneous portion 20 of the port unit 10 comprises a firstsubstantially cylindrical part 26 that is connected to the secondsubstantially cylindrical part 28 by the elongate joining section 30. Asexplained below, the majority of the subcutaneous portion 20 is locatedin a recess formed in the skull bone. In particular, the majority of theelongate joining section 30 is buried within the slot or recess formedin the skull. Preferably, the elongate joining section 30 is sub-flushto the outer surface of the skull bone and bone chipping or the like areplaced on top of the elongate joining section 30 after implantation.This allows bone to regrow over the top of the elongate joining section30 after implantation. After such bone growth, the first substantiallycylindrical part 26 is separated from the second substantiallycylindrical part 28 by a region that is buried within the skull bone.This acts as a infection barrier between the supply tube connections andthe percutaneous part of the port unit 10 where infection is most likelyto occur. In other words, the arrangement reduces the chance of anyinfection that arises at the interface between the skin and theprotruding percutaneous portion 22 2 5 from passing to the supply tube14 and migrating along the outer surfaces of the various tubes that leadto the catheter devices that bypass the blood-brain barrier.Furthermore, the size of the percutaneous part of the port unit 10 isminimised thereby reducing the size of incision required thereby furtherreducing the infection risk.

In addition, it can be seen that the router unit 12 is located away fromthe port unit 10. In this example, the router unit 12 is separated fromthe port unit 10 by about 15 cm of dual-lumen tubing 14. As noted abovethe most likely infection site is the interface between the skin and thepercutaneous portion 22 of the port unit 10. Providing the router unit12 between the tubing from the port unit 10 and the catheter devices 18thus introduces a further barrier to infection.

Bacterial filters may be provided within the apparatus to remove anybacteria present in the carrier fluid or in the therapeutic agent thatis delivered. A bacterial filter may, for example, be located in theport unit 10 (e.g. in the second substantially cylindrical part 28)and/or in the router unit 12. The pump 2 may also or alternativelyinclude a bacterial filter. The apparatus may also comprise an airfilter to remove any air bubbles present in the fluid delivered to thebrain. Such air bubbles are most likely to arise at connections betweentubes or at the point of infusion of therapeutic agent into the portunit 10. In this example, the air filter is placed in the router unit 12so that it as close as possible to the catheter devices 18 therebyremoving as much air from the apparatus as possible. Alternatively, oradditionally, air filters may be provided in the port unit 10, forexample in the second substantially cylindrical part 28.

Referring to FIGS. 3 a-3 d, the internal configuration of thesubcutaneous portion 20 of the port unit 10 is shown. In particular,FIGS. 3 b, 3 c and 3 d are sections through the planes I-I, II-II andIII-III respectively that are shown in FIG. 3 a. As outlined above, thesubcutaneous portion 20 of the port unit 10 comprises a firstsubstantially cylindrical part 26 that is connected to a secondsubstantially cylindrical part 28 by an elongate joining section 30.

The inlet 8 provided on the second part 28, which receives fluid underpressure from the remotely located pump, is in fluid communication withan inflow conduit 50 that passes through the elongate joining section 30to the first part 26. Two outflow conduits 52 a and 52 b are also routedfrom the first part 26 back to the second part 28 via the elongatejoining section 30. The outflow conduits 52 a and 52 b are in fluidcommunication with lumens of the dual-lumen supply tube 14. The firstpart 26 also comprises two vertical channels 54 a and 54 b. The inflowconduit 50 is in fluid communication with each of the vertical channels54 a and 54 b via flow restricting channels 56 a and 56 b. Linkingchannels 58 a and 58 b provide fluid communication between the verticalchannels 54 a and 54 b and the respective outflow conduits 52 a and 52b.

The two vertical channels 54 a and 54 b are sealed at one end by arubber bung 60 which may be provided as part of the percutaneous portion22 of the port unit 10; the rubber bung 60 is shown in FIG. 3 d. Therubber bung 60 permits fluid delivery needles 62 a and 62 b to enter thevertical channels 54 a and 54 b respectively. When a fluid deliveryneedle is inserted into its associated vertical channel, the flow ofcarrier fluid into that vertical channel is substantially blocked.Instead, fluid expelled from the needle tip passes through theassociated linking channel and outflow conduit to the attached catheterdevice. It should be noted that such an arrangement permits the type,amount and flow rate of the therapeutic agent delivered via eachcatheter device to be separately controlled. In the absence of aninserted fluid deliver needle, the flow restricting channels 56 a and 56b dispense carrier fluid into the respective vertical channels. The flowrestricting channels 56 a and 56 b also perform the function ofproviding separate flow control over the amount of carrier fluid thatpasses to each catheter device. Although needle/septum based fluidconnections are described above, it should be noted that needlelessfluid connections could alternatively be provided.

It should be noted that although the above described example illustratesa port unit suitable for delivering fluid to two catheter devices,similar port units may be fabricated for use with fewer or more catheterdevices. Furthermore, although continuous flush through of a carrierfluid is advantageous in certain applications (for example when usingvery fine catheters that may otherwise become occluded) it is notessential. A port unit similar to that described above but without theinlet for the carrier fluid could thus be provided.

Referring to FIG. 4, a port unit 110 is illustrated for use without acontinuous supply of carrier fluid. The port 110 comprises asubcutaneous portion 120 and a percutaneous portion 122 that has anextracorporeal surface 124. The subcutaneous portion 120 comprises afirst substantially cylindrical part 126 that is connected to a secondsubstantially cylindrical part 128 by the elongate joining section 130.The proximal end of a four lumen supply tube 114 protrudes from thesecond part 128. The distal end of the four lumen supply tube 114 mayterminate at a router unit (not shown) to which four separate catheterdevices (not shown) are connected. Lips 125 for engaging the surface ofthe bone around a recess formed in the bone are also provided.

The first substantially cylindrical part 126 comprises four verticalinternal channels that are in separate fluid with four conduits thatpass from the first part 126 to the second part 128 through the elongatejoining section 130. The four conduits are in separate fluidcommunication with respective lumen of the four lumen supply tube 114.The percutaneous portion 122 of the port unit 110 comprises a rubberbung (not shown) that seals one end of the vertical channel. A fluiddelivery needle may be inserted through the rubber bung into any one ormore of the vertical channels thereby permitting fluid to be pumpedalong each conduit to the associated catheter device. In this manner,fluid may be supplied to the required catheter device or devices as andwhen required.

It can thus be seen that the port unit 110 is similar to the port unit10 described with reference to FIGS. 1 to 3, but does not comprise aninlet for providing the continuous supply of carrier fluid from anabdominal pump. Apparatus comprising the port 110 may be used withcatheters having a sufficiently large diameter to prevent occlusion orif acute or short term infusion is required.

Referring to FIGS. 5 a-5 c, a method will be described for moulding aport unit such as that shown in FIG. 4 from a plastic material, such asPEEK.

FIG. 5 a shows a moulded plastic subcutaneous portion 150 of the portunit that comprises a first part 152, a second part 154 and a elongatesection 156 that joins the first and second parts. During the mouldingprocess, four wires 158 extend through the subcutaneous portion 150 toform four fluid conduits. Four needles 160, which each intersect one ofthe wires 158, provide the vertical channels. After moulding, the wires158 and needles 160 are withdrawn to form the required conduits andchannels respectively. An over-moulded or sheathed four lumen supplytube 162 can then be attached to the second part 154 of the port unit.The outer sheath of the supply tube 162 is secured in place by a lockingscrew 166. Prior to securing the sheath in place, a fluidic connectionis provided between each lumen of the supply tube 162 and one of theconduits within the port. As described above, the distal end of thesupply tube 162 may be connected to a router unit 168

As shown in FIG. 5 b, a percutaneous portion 180 may then be attached,for example using laser welding, to the surface of the first part 152 ofthe subcutaneous portion 150. The end of the conduits 190 formed duringmoulding are also sealed using plugs 188. The percutaneous portion 180includes a rubber bung 182 that seals the ends of the four verticalchannels 184 formed in the first part 152 of the subcutaneous portion150. The percutaneous portion 180 also comprises an extracorporealsurface 186 having four access holes that each allow a needle to bepassed through the rubber bung 182 into an associated one of thevertical channels 184.

FIG. 5 c shows the port unit after the step of plasma spraying a layerof titanium 200 onto the lower part 194 of the port unit. This plasmaspraying step may be followed by a step of applying a layer ofhydroxy-apatite. It should be noted that the upper part 196 of thepercutaneous portion 180 is masked during this procedure and istherefore not coated with the titanium or hydroxy-apatite. This upperpart 196 may comprise a diamond like coating (DLC) 192 that provides asmooth surface or it can be made from a smooth material such astitanium.

As explained above the subcutaneous portion 150 osseointegrates with theskull bone 193 into which it is embedded; this is shown in the inset toFIG. 5 c. As also shown in the inset to FIG. 5 c, the lower part 194 ofthe port unit extends so that the dermis 195 (which may also be thinnedto provide an improved interface between the dermis and the periosteum)grows into or bio-integrates with its roughened surface. The epidermis197 of the skin is arranged to lie adjacent the smooth surface of theupper part 196 but does not adhere to that surface. Regular cleaning ofthe upper (smooth) part of the percutaneous portion 180 may be performedto ensure no tissue adheres thereto. This arrangement ensures the portunit is not marsupialised and also reduces the risk of infection.

It is important to note that many other techniques or variants of theabove described technique may be used to form port units as describedherein. In particular, the skilled person would be aware of the variousways in which such port units could be manufactured in a reliable andcost effective manner.

FIG. 6 shows an implantation aid 250 that is designed to facilitateimplantation of the above described port units (e.g. a port unit 10 or110). The implantation aid 250 comprises an oval metal block 252 havinga pair of flanges 254 and a plurality of bone pins 256 provided at alower (skull facing) surface 258. The implantation aid 250 can thus betemporarily affixed to skull by bone screws 260 passed through holes inthe flanges 254. The metal block 252 also includes a pair of drill guideholes 262 that can receive removable drill hole sleeves 266 and aninterconnecting metal slot 264. The dimensions and spacing of the drillhole sleeves, guide holes 262 and slot 264 correspond to the dimensionsof the port unit that is to be attached to the skull. As will bedescribed below, the implantation aid 250 allows the skull to be cutusing cutting tools so as to form a recess that is shaped to receive thesubcutaneous portion of the port unit.

Referring to FIGS. 7 a to 7 g, a surgical method will be described forimplanting neurological apparatus comprising a port unit and a routerunit as described with reference to FIGS. 1-3 using the implantation aiddescribed with reference to FIG. 6.

FIG. 7 a shows a first step in the method of marking out a flap 300behind the ear of a subject using a template. The scalp is alsopunctured at position 302 in a manner that marks the skull bone. Alarger flap 304 is also made at the site where the catheter burr holesand router unit are to be located. FIG. 7 b shows the flap 300 afterbeing turned over. The subdermal tissue is also removed at this stage.

FIG. 7 c illustrates the implantation aid 250 described with referenceto FIG. 6 attached to the skull by bone screws 260. The alignment aid250 is located in position using the puncture mark made in the skull asreference mark. The drill hole sleeves 266 are placed in the drill guideholes 262 and a drill 310 is passed through each of the holes in turn toform two holes in the skull. Each drilled hole has a depth of around 5mm.

FIG. 7 d shows the step, which is performed after removing the drillhole sleeves 266 from the drill guide holes 262, of cutting anapproximately 1 mm wide trench using an oscillating saw 320. Theimplantation aid 250 is then detached from the skull. FIG. 7 e shows thenext step of using a 2 mm burr device 330 to widen the distal slot 331to approximately 2 mm.

FIG. 7 f then shows the step of using an impactor 340, to which a portunit 110 as described with reference to FIG. 4 is attached, to tap thatport unit 110 into a snug engagement with the appropriately shaped hole342 in the skull. A router unit 344 and catheters 350 can also beimplanted at this stage.

Finally, as shown in FIG. 7 g, the impactor 340 is disconnected from theport unit 110 and the slots 352 are backfilled with bone chippings. Itcan then be seen that the subcutaneous portion 120 of the port unit 110is buried substantially within the skull bone and that the percutaneousportion 122 will protrude through the skin of the scalp to provide theextracorporeal surface 124.

The above described surgical implantation method is merely one exampleof how the port unit could be surgically implanted and the skilledperson would appreciate that numerous variations of the above method arepossible. For example, a linear incision or an L-shaped (hockey stick)incision could be made in the skin instead of forming a skin flap asdescribed above. The skin could then be thinned on either side of theincision and enough skin removed to accommodate the percutaneous portion180 of the port unit. The port unit may also be mounted to other areasof the head or to a different bone in the body. For example, the portunit could be mounted to the sternum if delivery of therapeutic agentsto the spinal cord was required. It would also be possible to mount thedevice within the mouth (e.g. to the jaw bone). A mouth mounted devicemay take the form of a (e.g. ceramic) tooth or pass through a tooth.

The examples described above with reference to FIGS. 1 to 7 describeport units that comprise two substantially cylindrical parts joined byan elongate joining section. Such port units can be securely affixed tothe skull and provide a barrier to infection reaching the implantedcatheter device from the percutaneous part of the port unit.

FIG. 8 illustrates neurological apparatus comprising a port unit 410connected to a router unit 412 by a four lumen supply tube 414.Intraparenchymal catheter devices 418 are connected to the router unit412. The router unit 412 also comprises a bacterial filter.

Referring to FIG. 9 a, the port unit 410 that is illustrated in FIG. 8is shown in more detail. The port unit 410 comprises a subcutaneousportion 420 and a percutaneous portion 422 that has an extracorporealsurface 424. The subcutaneous portion 420 comprises a plurality ofprotruding broaching fins 421 that run along the majority of its length.The subcutaneous portion 420 also comprises a first substantiallycylindrical part 426 from which an elongate section 430 protrudes. Thedistal end of the elongate section 430 comprises four protruding rigidtubes 432 for engaging and providing a separate fluidic link with eachof the four lumens 434 of the supply tube 414. The percutaneous portion422 include a rubber bung accessible from the extracorporeal surface 424that seals four separate fluidic channels through the port unit 410.Insertion of fluid delivery needles through the rubber bung providesfluid access to the separate fluidic channels of the port unit therebypermitting fluid to be pumped to attached catheter devices via thesupply tube 414 and router unit 412.

FIG. 9 b shows a side view of the port unit 410 implanted in a keyshaped recess 442 as shown in FIG. 9 c that is formed in the skull bone440 of a subject. Implantation may be performed by forcing the port unit410 into the recess using an impactor or the like, thereby causing thefins 421 to cut into the bone and thus affixing the port unit in place.The key-like shape of the port unit in combination with the fins 421acts to secure the port unit 410 in place and prevents any unwantedmovement (e.g. rotation) thereof. The majority of the subcutaneousportion 422 is located below the outer surface of the skull bone 440whilst the percutaneous portion 422 passes through a hole in the skinThe elongate section 430 of the port unit 410 and the proximal end ofthe supply tube 414 are also buried below the outer surface of the skullin an aperture that is back filled with bone chippings 444. The dermisof the skin 446 seals against the roughened surfaces of the subcutaneousportion 422 and percutaneous portion 422. It is also noted that thehypodermis or subdermal tissue 448 is thinned in the region of port unitimplantation thereby allowing a living seal to be provided between thedermis and the periosteum.

It should also be noted that it would be possible to integrate thesupply tube 414 with the elongate section 430 of the port unit 410. Forexample, the proximal end of a supply tube could protrude directly fromthe first substantially cylindrical part 426 to form the buried elongatesection of the subcutaneous portion 422.

FIGS. 10 to 12 show further neurological apparatus that comprises a portunit 510, a supply tube 514, a router unit 512 and four catheter devices518. In particular, FIG. 10 shows the apparatus implanted in a subject,FIG. 11 illustrates the apparatus prior to implantation and FIG. 12 showthe components of the filter unit in more detail.

Referring to FIGS. 10 and 11, it can be seen how the port unit 510 isconnected to the router unit 512 by the supply tube 514. The catheterdevices 518 are each linked to an outlet of the router unit. The portunit 510 is analogous to the port unit 410 described above withreference to FIGS. 8 and 9 a-9 c. The router unit 512, however, providesan air filtering function.

Referring to FIG. 12, the structure of the router unit 512 is shown inmore detail. The router unit 512 comprises a four chamber outflowportion 520, a hydrophilic (bacterial) filter 522, a four chamber inflowportion 524, a hydrophobic filter 526 and a diaphragm membrane 528. Asdescribed in more detail below, fluid passed to the router unit 512through the four lumens of the supply tube 514 is separately filteredand output via outlets 530 to the respective catheter devices 518. Inother words, each fluid path through the router unit is separatelyfiltered and there is no mixing of the fluid that is routed to thedifferent catheter devices 518.

In operation, fluid from each lumen of the supply tube 514 passes to arespective one of the inflow chambers of the inflow portion 524. Theliquid of the fluid is attracted to the hydrophilic filter 522 andpasses through that hydrophilic filter 522 into the associated outflowchamber of the outflow portion 520. Gas (e.g. air) does not pass throughthe hydrophilic filter 522. Fluid from each chamber of the outflowportion 520 passes to an outlet 530 that is in turn connected to acatheter device 518. The hydrophobic filter 526 acts as a barrier toliquid, but allows any gas (e.g. air) bubbles to pass through it. Gas(e.g. air) is thus removed from the fluid and is allowed to dissipatethrough the diaphragm membrane 528 into the body. The hydrophilic filter522 may also be configured to provide a bacterial filtration function.

As can be seen from FIG. 10, the router unit 512 is located as close tothe catheter devices 518 as possible. This ensures air removal isperformed as far downstream as possible thereby minimising the amount ofair that is present in the fluid expelled from the catheter devices 518.In particular, the air filtration is performed away from the port unit510 and the majority of the tube connections that could introduce air.

Referring to FIG. 13, a further embodiment of neurological apparatus ofthe present invention is shown. The apparatus comprises an abdominallyimplantable constant pressure pump 602, a percutaneous port unit 610, arouter unit 612 and catheter device 618. A single lumen supply tube 606supplies carrier fluid from the pump 602 to the router unit 612. A fourlumen supply tube 614 provide four separate fluid pathways from the portunit 610 to the router unit 612. The port unit 610 is preferably a portunit of the type described with reference to FIG. 4. The apparatus isarranged so that a flow of fluid supplied by the abdominal pump 602 iscontinuously pumped, at a low flow rate, to the catheter devices 618 toprevent occlusion of such devices. Fluid containing a therapeutic agentmay also be pumped into the port unit 610 and directed to each catheterdevice 618 via the router unit 612. The router unit 612 includes abacterial filter and/or an air filter.

FIG. 14 illustrates a variant of the device described with reference toFIG. 13. Carrier fluid from an abdominal pump 602 is pumped to a filterunit 620 via a single lumen supply tube 606. The filter unit 620 splitsthe received carrier fluid into four streams that are routed into thefour lumens at the proximal end of the supply tube 622. At the distalend of the supply tube 622, the four lumens separate into four separatetubes that are each connected to a catheter device 618. The port unit610 is connected to the filter unit 620 by a four lumen supply tube 624and provides four separate fluidic links to the four separate fluidstreams through the filter unit 620. Therapeutic agent may thus bepumped to any one of the catheter devices 618 from the port unit 610.

FIG. 15 illustrates an alternative arrangement to that shown in FIG. 13.Instead of an abdominal pump being used to supply a constant flow ofcarrier fluid, a ventricular shunt 640 and pump 642 are insteadprovided. In this arrangement, a constant flow of cerebrospinal fluid(CSF) is passed to the router unit 612 instead of a supply of carrierfluid.

The above described percutaneous fluid port devices can be press fittedinto appropriate recesses form in the skull. A number of alternativeanchoring arrangement may be used to affix a port units to the skullbone.

FIGS. 16 and 17 illustrate a port unit 710 having a protrudingcylindrical portion 712 that engages a complimentary recess 714 formedin a bone 716. As shown in the upper inset of FIG. 16, the cylindricalportion 712 includes perforations 718. As shown in the lower inset ofFIG. 16, a complementary circular trench or recess 714 may be formed inthe bone, optionally including a central circular island 720. If acircular hole is formed (i.e. without the central circular island 720)bone chippings may be used to fill the internal cavity of thecylindrical portion 712. FIG. 17 illustrates the device of FIG. 16 whenfixed in place. Again, the port unit 710 has an extracorporeal surface724 that allows access to ports or fluid channels that exit the unitsubcutaneously.

Supply tubing 730 may be routed through a slot formed in the cylindricalportion 712. Such supply tubing 730 may be buried, at least partially,within a trench formed in the bone. For example, the proximal end of thesupply tubing 730 may form an elongate section that is buried in thebone in a similar manner to that described above.

Referring next to FIGS. 18 to 20, a variant of the port described abovewith reference to FIGS. 1 to 3 is shown.

FIG. 18 is a cross-section showing the components of the valved portunit 800. The valved port unit 800 comprises a washer 802 and gasket 804that are constrained by a hypotube 806 but are otherwise free to movewithin the cavity. A septum 808 is also provided. The port unit 800 isshown in FIG. 18 when in a first state that allows fluid to flow fromthe inlet 818 to the outlet 820. In particular, it can be seen thatwithout the gasket 804 blocking the inlet channel 810, liquid receivedunder pressure at the inlet 818 can flow to the outlet 820.

FIG. 19 shows the valved port unit 800 when a hollow needle 830 isinserted through the septum 808 thereby pushing down on the washer 802.In this second state, the washer 802 compresses the gasket 804 therebyblocking the egress of fluid from the inlet channel 810. The fluid pathfrom the inlet 818 to the outlet 820 is thus obstructed. Instead, fluiddispensed through the inserted needle 830 can be pumped to the outlet820 and onward to implanted catheter device.

FIG. 20 shows an exploded view of the internal components of the valvedport unit 800. The valved port unit 800 may, in common with the portunit described above, have a subcutaneous portion that can be located ina recess formed in bone and a percutaneous portion protruding therefrom.

It should again be remembered that the above examples are merelyillustrative of the present invention. Port units having a single port,two ports or four ports are described in detail above, but the inventionis equally applicable to port units having a different number of ports.Furthermore, the methods of manufacturing the port units and the way inwhich they are implanted are merely illustrative. The use of a widevariety of manufacturing and/or implantation techniques would bepossible. Furthermore, although the above devices are described for usein delivering fluid into the body, it should be noted that such devicescould also be used as shunts for extracting fluid from the body. Thepercutaneous fluid delivery device described in detail above could thusbe used as a percutaneous fluid delivery or fluid extraction device.

1. An implantable percutaneous fluid delivery device comprising: asubcutaneous base portion comprising one or more ports for supplyingfluid to one or more implanted catheter devices, and a percutaneousportion comprising an extracorporeal surface, the one or more ports ofthe subcutaneous base portion being accessible from the extracorporealsurface of the percutaneous portion, wherein the subcutaneous baseportion is at least partially insertable into a complementary recessformed in a bone, the complementary recess having an internal surfaceand the subcutaneous base portion comprising one or more features forgripping the internal surface of the complementary recess therebydirectly anchoring the subcutaneous base portion to the bone.
 2. Thedevice according to claim 1, wherein the one or more features enable thesubcutaneous base portion to be retained in the complementary recess bya friction fit.
 3. The device according to claim 1, wherein the one ormore features comprise one or more protrusions provided on an outersurface of the subcutaneous base portion, the one or more protrusionsallowing the device to be secured in the complementary recess by apush-fit action.
 4. The device according to claim 1, wherein thesubcutaneous base portion comprises at least one of a rough surface anda coating that promotes osseointegration.
 5. The device according toclaim 1, wherein the subcutaneous base portion comprises a protrudinglip for engaging an outer surface of a bone around the periphery of arecess formed in that bone.
 6. The device according to claim 1, whereinthe subcutaneous base portion comprises a first part that is attachableto the percutaneous portion and an elongate section that protrudes fromthe first part, wherein, when the device is implanted in the body, awhole of the elongate section is located within a recess formed in thebone.
 7. The device according to claim 6, wherein the subcutaneous baseportion comprises a second part, the first and second parts beingconnected by the elongate section.
 8. The device according to claim 6,wherein the elongate section is at least 10 mm long.
 9. The deviceaccording to claim 1, comprising two or more ports.
 10. The deviceaccording to claim 1, comprising at least one of a bacterial filter andan air vent.
 11. The device according to claim 1, wherein thesubcutaneous base portion comprises at least one subcutaneous fluidinlet for receiving fluid from at least one remotely implanted pump,wherein fluid received at the at least one subcutaneous fluid inlet isroutable to the one or more ports.
 12. The device according to claim 1,wherein at least part of the percutaneous portion comprises a peripheralsurface that encourages tissue ingrowth.
 13. A Neurological apparatuscomprising; an implantable percutaneous fluid delivery device accordingto claim 1, a supply tube having one or more lumens, an implantablerouter unit having one or more inlets for routing fluid to one or moreoutlets, and one or more intraparenchymal catheter devices, wherein theone or more ports of the percutaneous fluid delivery device areconnected to the one or more inlets of the router unit via the supplytube and the one or more intraparenchymal catheter devices are connectedto the one or more outlets of the implantable router unit.
 14. Theapparatus according to claim 13, comprising a external fluid connectorunit for cooperating with the extracorporeal surface of the percutaneousfluid delivery device to provide fluid communication with the ports. 15.A jig for implanting a percutaneous fluid delivery device of claim 1,wherein the jig provide a template for cutting a recess in bone intowhich the subcutaneous base portion of the percutaneous fluid deliverydevice can be fitted.
 16. An implantable percutaneous fluid deliverydevice comprising: a subcutaneous base portion comprising one or moreports for supplying fluid to one or more implanted catheter devices, anda percutaneous portion comprising an extracorporeal surface, the one ormore ports of the subcutaneous base portion being accessible from theextracorporeal surface of the percutaneous portion, wherein thesubcutaneous base portion is at least partially insertable into acomplementary recess formed in a bone and at least part of thesubcutaneous base portion osseointegrates following implantation. 17.The device according to claim 16, wherein the subcutaneous base portioncomprises at least one of a rough surface and a coating that promotesosseointegration.